Steven injured his foot at Thursday training and will not train for a month.
The Saints expect him to be out of action for eight to 10 weeks.
The midfielder has a fracture of the sesamoid bone in his right foot, but will not need surgery.
"Jack has been training strongly throughout the pre-season, but pulled up sore after training today," Saints head of football Chris Pelchen said in a club statement.
"Scans conducted late this afternoon revealed a fracture in his right foot.
"It's important to note that the fracture is not stress related and followed an innocuous incident during training."
The Saints have had a tough off-season, with coach Scott Watters sacked last year and replaced by Alan Richardson.
Steven is the second top St Kilda midfielder who will definitely miss the start of their season.
Veteran Leigh Montagna is also out of the round-one game against Melbourne because of a carry-over suspension from last year.
Steven, 23, has played 73 games since his 2009 debut and last year was the first time he has won the club's best and fairest award.
Defender Sam Gilbert is also unlikely to be ready for round one as he recovers from foot surgery.
The Saints will welcome back several key players in Saturday's pre-season game against Greater Western Sydney.
Captain Nick Riewoldt, Lenny Hayes, Sean Dempster and James Gwilt will return for the Wagga match.